6oze

From Proteopedia

Crystal structure of the catalytic domain of human Endonuclease V (C140S/C225S/C226A/C228S)

PDB ID 6oze

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Structural highlights

6oze is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.5Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ENDOV_HUMAN Endoribonuclease that specifically cleaves inosine-containing RNAs: cleaves RNA at the second phosphodiester bond 3' to inosine. Has strong preference for single-stranded RNAs (ssRNAs) toward double-stranded RNAs (dsRNAs). Cleaves mRNAs and tRNAs containing inosine. Also able to cleave structure-specific dsRNA substrates containing the specific sites 5'-IIUI-3' and 5'-UIUU-3'. Inosine is present in a number of RNAs following editing; the function of inosine-specific endoribonuclease is still unclear: it could either play a regulatory role in edited RNAs, or be involved in antiviral response by removing the hyperedited long viral dsRNA genome that has undergone A-to-I editing. Binds branched DNA structures.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Endonuclease V (EndoV) cleaves the second phosphodiester bond 3' to a deaminated adenosine (inosine). Although highly conserved, EndoV homologs change substrate preference from DNA in bacteria to RNA in eukaryotes. We have characterized EndoV from six different species and determined crystal structures of human EndoV and three EndoV homologs from bacteria to mouse in complex with inosine-containing DNA/RNA hybrid or double-stranded RNA (dsRNA). Inosine recognition is conserved, but changes in several connecting loops in eukaryotic EndoV confer recognition of 3 ribonucleotides upstream and 7 or 8 bp of dsRNA downstream of the cleavage site, and bacterial EndoV binds only 2 or 3 nt flanking the scissile phosphate. In addition to the two canonical metal ions in the active site, a third Mn(2+) that coordinates the nucleophilic water appears necessary for product formation. Comparison of EndoV with its homologs RNase H1 and Argonaute reveals the principles by which these enzymes recognize RNA versus DNA.

Evolution of Inosine-Specific Endonuclease V from Bacterial DNase to Eukaryotic RNase.,Wu J, Samara NL, Kuraoka I, Yang W Mol Cell. 2019 Oct 3;76(1):44-56.e3. doi: 10.1016/j.molcel.2019.06.046. Epub 2019, Aug 20. PMID:31444105^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Fladeby C, Vik ES, Laerdahl JK, Gran Neurauter C, Heggelund JE, Thorgaard E, Strom-Andersen P, Bjoras M, Dalhus B, Alseth I. The human homolog of Escherichia coli endonuclease V is a nucleolar protein with affinity for branched DNA structures. PLoS One. 2012;7(11):e47466. doi: 10.1371/journal.pone.0047466. Epub 2012 Nov 5. PMID:23139746 doi:http://dx.doi.org/10.1371/journal.pone.0047466
↑ Vik ES, Nawaz MS, Strom Andersen P, Fladeby C, Bjoras M, Dalhus B, Alseth I. Endonuclease V cleaves at inosines in RNA. Nat Commun. 2013;4:2271. doi: 10.1038/ncomms3271. PMID:23912683 doi:http://dx.doi.org/10.1038/ncomms3271
↑ Morita Y, Shibutani T, Nakanishi N, Nishikura K, Iwai S, Kuraoka I. Human endonuclease V is a ribonuclease specific for inosine-containing RNA. Nat Commun. 2013;4:2273. doi: 10.1038/ncomms3273. PMID:23912718 doi:http://dx.doi.org/10.1038/ncomms3273
↑ Wu J, Samara NL, Kuraoka I, Yang W. Evolution of Inosine-Specific Endonuclease V from Bacterial DNase to Eukaryotic RNase. Mol Cell. 2019 Oct 3;76(1):44-56.e3. doi: 10.1016/j.molcel.2019.06.046. Epub 2019, Aug 20. PMID:31444105 doi:http://dx.doi.org/10.1016/j.molcel.2019.06.046